Abstract: Thrombospondin-1 (TSP-1), a matricellular protein widely acclaimed to be involved in the inhibition of angiogenesis and tumorigenesis, is synthesized and secreted by many cell types, including osteoblast and cancer cells. TSP-1 is highly upregulated during early stage of osteogenesis, whereas it inhibits terminal osteoblast differentiation. Expression of TSP-1 is downregulated in cancer cells, and its ectopic expression has been shown to restrain tumor growth. Transcriptional regulation of TSP-1 in osteogenesis and cancer is poorly understood; this prompted us to study its regulation by the two key regulators of the aforementioned processes: Runx2 and Runx3. Through a PCR-based cDNA subtraction technique, we identified and cloned a cDNA fragment for mouse TSP-1, whose expression was dramatically upregulated in response to Runx2 expression in mesenchymal stem cells. Moreover, TSP-1 expression was considerably reduced in the lung of Runx2 knockout mouse. On the other hand, TSP-1 gene expression drastically increased at both the transcriptional and translational levels in response to Runx3 expression in B16-F10 melanoma cells. In line with this, Runx2 and Runx3 bound to the TSP-1 promoter and stimulated its activity. Hence, these results provide first line of evidence that TSP-1 is a transcriptional target gene of Runx2 and Runx3.
Keywords: TSP-1; Runx2; Runx3; C3H10T1/2 stem cells; osteoblast; metastasis; cancer; melanoma; B16-F10; angiogenesis
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Shi, X.; Deepak, V.; Wang, L.; Ba, X.; Komori, T.; Zeng, X.; Liu, W. Thrombospondin-1 Is a Putative Target Gene of Runx2 and Runx3. Int. J. Mol. Sci. 2013, 14, 14321-14332.
Shi X, Deepak V, Wang L, Ba X, Komori T, Zeng X, Liu W. Thrombospondin-1 Is a Putative Target Gene of Runx2 and Runx3. International Journal of Molecular Sciences. 2013; 14(7):14321-14332.
Shi, Xiuming; Deepak, Vishwa; Wang, Linghui; Ba, Xueqing; Komori, Toshihisa; Zeng, Xianlu; Liu, Wenguang. 2013. "Thrombospondin-1 Is a Putative Target Gene of Runx2 and Runx3." Int. J. Mol. Sci. 14, no. 7: 14321-14332.